Martin Enwerem

Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30-60) days and 60 (33-90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related.Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions.

The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts. The core published documents and guidelines have been reviewed, including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines. After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities.

Coronavirus disease has disrupted tuberculosis services globally. Data from 33 centers in 16 countries on 5 continents showed that attendance at tuberculosis centers was lower during the first 4 months of the pandemic in 2020 than for the same period in 2019. Resources are needed to ensure tuberculosis care continuity during the pandemic.

South African patients with rifampicin-resistant tuberculosis (TB) and resistance to fluoroquinolones and/or injectable drugs (extensively drug-resistant (XDR) and preXDR-TB) were granted access to bedaquiline through a clinical access programme with strict inclusion and exclusion criteria. PreXDR-TB and XDR-TB patients were treated with 24 weeks of bedaquiline within an optimised, individualised background regimen that could include levofloxacin, linezolid and clofazimine as needed. 200 patients were enrolled: 87 (43.9%) had XDR-TB, 99 (49.3%) were female and the median age was 34 years (interquartile range (IQR) 27–42). 134 (67.0%) were living with HIV; the median CD4 + count was 281 cells·μL −1 (IQR 130–467) and all were on antiretroviral therapy. 16 out of 200 patients (8.0%) did not complete 6 months of bedaquiline: eight were lost to follow-up, six died, one stopped owing to side effects and one was diagnosed with drug-sensitive TB. 146 out of 200 patients (73.0%) had favourable outcomes: 139 (69.5%) were cured and seven (3.5%) completed treatment. 25 patients (12.5%) died, 20 (10.0%) were lost from treatment and nine (4.5%) had treatment failure. 22 adverse events were attributed to bedaquiline, including a QT interval corrected using the Fridericia formula (QTcF) >500 ms (n=5), QTcF increase >50 ms from baseline (n=11) and paroxysmal atrial flutter (n=1). Bedaquiline added to an optimised background regimen was associated with a high rate of successful treatment outcomes for this preXDR-TB and XDR-TB cohort.